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Baluk, P. et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J. Exp. Med. 204, 2349-2362

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Journal of Experimental Medicine (Impact Factor: 13.91). 11/2007; 204(10):2349-62. DOI: 10.1084/jem.20062596
Source: PubMed

ABSTRACT Recirculation of fluid and cells through lymphatic vessels plays a key role in normal tissue homeostasis, inflammatory diseases, and cancer. Despite recent advances in understanding lymphatic function (Alitalo, K., T. Tammela, and T.V. Petrova. 2005. Nature. 438:946-953), the cellular features responsible for entry of fluid and cells into lymphatics are incompletely understood. We report the presence of novel junctions between endothelial cells of initial lymphatics at likely sites of fluid entry. Overlapping flaps at borders of oak leaf-shaped endothelial cells of initial lymphatics lacked junctions at the tip but were anchored on the sides by discontinuous button-like junctions (buttons) that differed from conventional, continuous, zipper-like junctions (zippers) in collecting lymphatics and blood vessels. However, both buttons and zippers were composed of vascular endothelial cadherin (VE-cadherin) and tight junction-associated proteins, including occludin, claudin-5, zonula occludens-1, junctional adhesion molecule-A, and endothelial cell-selective adhesion molecule. In C57BL/6 mice, VE-cadherin was required for maintenance of junctional integrity, but platelet/endothelial cell adhesion molecule-1 was not. Growing tips of lymphatic sprouts had zippers, not buttons, suggesting that buttons are specialized junctions rather than immature ones. Our findings suggest that fluid enters throughout initial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics.

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    • "To understand whether ANG2 regulates this transformation process, we treated pregnant females with the ANG2- blocking antibody starting from E12.5, before the transformation occurs, and analyzed the embryos at E18.5. At the sprouting vessel front, junctions in the IgG-treated lymphatics were zippers (Fig. 2A,B), consistent with the junctional pattern at the sprouting front reported elsewhere (Baluk et al. 2007; Yao et al. 2012), and ANG2 blockade did not affect this pattern (Fig. 2C,D). In the IgGtreated initial lymphatics behind the sprouts, the LEC shape was less elongated, and the junctions were clearly button-like (Fig. 2E,F). "
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